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Several recent fMRI studies of episodic and working memory representations converge on the finding that visual information is most strongly represented in occipito-temporal cortex during the encoding phase but in parietal regions during the retrieval phase. It has been suggested that this location shift reflects a change in the content of representations, from predominantly visual during encoding to primarily semantic during retrieval. Yet, direct evidence on the nature of encoding and retrieval representations is lacking. It is also unclear how the representations mediating the encoding-retrieval shift contribute to memory performance. To investigate these two issues, in the current fMRI study, participants encoded pictures (e.g., picture of a cardinal) and later performed a word recognition test (e.g., word "cardinal"). Representational similarity analyses examined how visual (e.g., red color) and semantic representations (e.g., what cardinals eat) support successful encoding and retrieval. These analyses revealed two novel findings. First, successful memory was associated with representational changes in cortical location (from occipito-temporal at encoding to parietal at retrieval) but not with changes in representational content (visual vs. semantic). Thus, the representational encoding-retrieval shift cannot be easily attributed to a change in the nature of representations. Second, in parietal regions, stronger representations predicted encoding failure but retrieval success. This encoding-retrieval "flip" in representations mimics the one previously reported in univariate activation studies. In summary, by answering important questions regarding the content and contributions to the performance of the representations mediating the encoding-retrieval shift, our findings clarify the neural mechanisms of this intriguing phenomenon., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

The hippocampus plays a central role as a coordinate system or index of information stored in neocortical loci. Nonetheless, it remains unclear how hippocampal processes integrate with cortical information to facilitate successful memory encoding. Thus, the goal of the current study was to identify specific hippocampal-cortical interactions that support object encoding. We collected fMRI data while 19 human participants (7 female and 12 male) encoded images of real-world objects and tested their memory for object concepts and image exemplars (i.e., conceptual and perceptual memory). Representational similarity analysis revealed robust representations of visual and semantic information in canonical visual (e.g., occipital cortex) and semantic (e.g., angular gyrus) regions in the cortex, but not in the hippocampus. Critically, hippocampal functions modulated the mnemonic impact of cortical representations that are most pertinent to future memory demands, or transfer-appropriate representations Subsequent perceptual memory was best predicted by the strength of visual representations in ventromedial occipital cortex in coordination with hippocampal activity and pattern information during encoding. In parallel, subsequent conceptual memory was best predicted by the strength of semantic representations in left inferior frontal gyrus and angular gyrus in coordination with either hippocampal activity or semantic representational strength during encoding. We found no evidence for transfer-incongruent hippocampal-cortical interactions supporting subsequent memory (i.e., no hippocampal interactions with cortical visual/semantic representations supported conceptual/perceptual memory). Collectively, these results suggest that diverse hippocampal functions flexibly modulate cortical representations of object properties to satisfy distinct future memory demands. Significance Statement The hippocampus is theorized to index pieces of information stored throughout the cortex to support episodic memory. Yet how hippocampal processes integrate with cortical representation of stimulus information remains unclear. Using fMRI, we examined various forms of hippocampal-cortical interactions during object encoding in relation to subsequent performance on conceptual and perceptual memory tests. Our results revealed novel hippocampal-cortical interactions that utilize semantic and visual representations in transfer-appropriate manners: conceptual memory supported by hippocampal modulation of frontoparietal semantic representations, and perceptual memory supported by hippocampal modulation of occipital visual representations. These findings provide important insights into the neural mechanisms underlying the formation of information-rich episodic memory and underscore the value of studying the flexible interplay between brain regions for complex cognition., (Copyright © 2023 the authors.)

Depending on a person's goals, different aspects of stored knowledge are accessed. Decades of behavioral work document the flexible use of knowledge, but little neuroimaging work speaks to these questions. We used representational similarity analysis to investigate whether the relationship between brain activity and semantic structure of statements varied in two tasks hypothesized to differ in the degree to which knowledge is accessed: judging truth (semantic task) and judging oldness (episodic task). During truth judgments, but not old/new recognition judgments, a left-lateralized network previously associated with semantic memory exhibited correlations with semantic structure. At a neural level, people activate knowledge representations in different ways when focused on different goals. The present results demonstrate the potential of multivariate approaches in characterizing knowledge storage and retrieval, as well as the ways that it shapes our understanding and long-term memory., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The "illusory truth" effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency, the subjective ease experienced while processing information, underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency.

Although it is known that brain regions in one hemisphere may interact very closely with their corresponding contralateral regions (collaboration) or operate relatively independent of them (segregation), the specific brain regions (where) and conditions (how) associated with collaboration or segregation are largely unknown. We investigated these issues using a split field-matching task in which participants matched the meaning of words or the visual features of faces presented to the same (unilateral) or to different (bilateral) visual fields. Matching difficulty was manipulated by varying the semantic similarity of words or the visual similarity of faces. We assessed the white matter using the fractional anisotropy (FA) measure provided by diffusion tensor imaging (DTI) and cross-hemispheric communication in terms of fMRI-based connectivity between homotopic pairs of cortical regions. For both perceptual and semantic matching, bilateral trials became faster than unilateral trials as difficulty increased (bilateral processing advantage, BPA). The study yielded three novel findings. First, whereas FA in anterior corpus callosum (genu) correlated with word-matching BPA, FA in posterior corpus callosum (splenium-occipital) correlated with face-matching BPA. Second, as matching difficulty intensified, cross-hemispheric functional connectivity (CFC) increased in domain-general frontopolar cortex (for both word and face matching) but decreased in domain-specific ventral temporal lobe regions (temporal pole for word matching and fusiform gyrus for face matching). Last, a mediation analysis linking DTI and fMRI data showed that CFC mediated the effect of callosal FA on BPA. These findings clarify the mechanisms by which the hemispheres interact to perform complex cognitive tasks., (Copyright © 2015 the authors 0270-6474/15/358191-10$15.00/0.)

Neurobiological memory models assume memory traces are stored in neocortex, with pointers in the hippocampus, and are then reactivated during retrieval, yielding the experience of remembering. Whereas most prior neuroimaging studies on reactivation have focused on the reactivation of sets or categories of items, the current study sought to identify cortical patterns pertaining to memory for individual scenes. During encoding, participants viewed pictures of scenes paired with matching labels (e.g., "barn," "tunnel"), and, during retrieval, they recalled the scenes in response to the labels and rated the quality of their visual memories. Using representational similarity analyses, we interrogated the similarity between activation patterns during encoding and retrieval both at the item level (individual scenes) and the set level (all scenes). The study yielded four main findings. First, in occipitotemporal cortex, memory success increased with encoding-retrieval similarity (ERS) at the item level but not at the set level, indicating the reactivation of individual scenes. Second, in ventrolateral pFC, memory increased with ERS for both item and set levels, indicating the recapitulation of memory processes that benefit encoding and retrieval of all scenes. Third, in retrosplenial/posterior cingulate cortex, ERS was sensitive to individual scene information irrespective of memory success, suggesting automatic activation of scene contexts. Finally, consistent with neurobiological models, hippocampal activity during encoding predicted the subsequent reactivation of individual items. These findings show the promise of studying memory with greater specificity by isolating individual mnemonic representations and determining their relationship to factors like the detail with which past events are remembered.

Voluntary episodic memories require an intentional memory search, whereas involuntary episodic memories come to mind spontaneously without conscious effort. Cognitive neuroscience has largely focused on voluntary memory, leaving the neural mechanisms of involuntary memory largely unknown. We hypothesized that, because the main difference between voluntary and involuntary memory is the controlled retrieval processes required by the former, there would be greater frontal activity for voluntary than involuntary memories. Conversely, we predicted that other components of the episodic retrieval network would be similarly engaged in the two types of memory. During encoding, all participants heard sounds, half paired with pictures of complex scenes and half presented alone. During retrieval, paired and unpaired sounds were presented, panned to the left or to the right. Participants in the involuntary group were instructed to indicate the spatial location of the sound, whereas participants in the voluntary group were asked to additionally recall the pictures that had been paired with the sounds. All participants reported the incidence of their memories in a postscan session. Consistent with our predictions, voluntary memories elicited greater activity in dorsal frontal regions than involuntary memories, whereas other components of the retrieval network, including medial-temporal, ventral occipitotemporal, and ventral parietal regions were similarly engaged by both types of memories. These results clarify the distinct role of dorsal frontal and ventral occipitotemporal regions in predicting strategic retrieval and recalled information, respectively, and suggest that, although there are neural differences in retrieval, involuntary memories share neural components with established voluntary memory systems.

Contralateral recruitment remains a controversial phenomenon in both the clinical and normative populations. To investigate the neural correlates of this phenomenon, we explored the tendency for older adults to recruit prefrontal cortex (PFC) regions contralateral to those most active in younger adults. Participants were scanned with diffusion tensor imaging and functional magnetic rresonance imaging during a lateralized word matching task (unilateral vs. bilateral). Cross-hemispheric communication was measured behaviorally as greater accuracy for bilateral than unilateral trials (bilateral processing advantage [BPA]) and at the neural level by functional and structural connectivity between contralateral PFC. Compared with the young, older adults exhibited 1) greater BPAs in the behavioral task, 2) greater compensatory activity in contralateral PFC during the bilateral condition, 3) greater functional connectivity between contralateral PFC during bilateral trials, and 4) a positive correlation between fractional anisotropy in the corpus callosum and both the BPA and the functional connectivity between contralateral PFC, indicating that older adults' ability to distribute processing across hemispheres is constrained by white matter integrity. These results clarify how older adults' ability to recruit extra regions in response to the demands of aging is mediated by existing structural architecture, and how this architecture engenders corresponding functional changes that allow subjects to meet those task demands.

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.

Major depressive disorder (MDD) is characterized by the presence of disturbances in emotional processing. However, the neural correlates of these alterations, and how they may be affected by therapeutic interventions, remain unclear. The present study addressed these issues in a preliminary investigation using functional magnetic resonance imaging (fMRI) to examine neural responses to positive, negative, and neutral pictures in unmedicated MDD patients (N = 22) versus controls (N = 14). After this initial scan, MDD patients were treated with cognitive behavioral therapy (CBT) and scanned again after treatment. Within regions that showed pre-treatment differences between patients and controls, we tested the association between pre-treatment activity and subsequent treatment response as well as activity changes from pre- to post-treatment. This study yielded three main findings. First, prior to treatment and relative to controls, patients exhibited overall reduced activity in the ventromedial prefrontal cortex (PFC), diminished discrimination between emotional and neutral items in the amygdala, caudate, and hippocampus, and enhanced responses to negative versus positive stimuli in the left anterior temporal lobe (ATL) and right dorsolateral PFC. Second, CBT-related symptom improvement in MDD patients was predicted by increased activity at baseline in ventromedial PFC as well as the valence effects in the ATL and dorsolateral PFC. Third, from pre- to post-treatment, MDD patients exhibited overall increases in ventromedial PFC activation, enhanced arousal responses in the amygdala, caudate, and hippocampus, and a reversal of valence effects in the ATL. The study was limited by the relatively small sample that was able to complete both scan sessions, as well as an inability to determine the influence of comorbid disorders within the current sample. Nevertheless, components of the neural networks corresponding to emotion processing disturbances in MDD appear to resolve following treatment and are predictive of treatment response, possibly reflecting improvements in emotion regulation processes in response to CBT., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Older adults, compared to younger adults, focus on emotional well-being. While the lifespan trajectory of emotional processing and its regulation has been characterized behaviorally, few studies have investigated the underlying neural mechanisms. Here, older adults (range: 59-73 years) and younger adults (range: 19-33 years) participated in a cognitive reappraisal task during functional magnetic resonance imaging (fMRI) scanning. On each trial, participants viewed positive, negative or neutral pictures and either naturally experienced the image ('Experience' condition) or attempted to detach themselves from the image ('Reappraise' condition). Across both age groups, cognitive reappraisal activated prefrontal regions similar to those reported in prior studies of emotion regulation, while emotional experience activated the bilateral amygdala. Psychophysiological interaction analyses revealed that the left inferior frontal gyrus (IFG) and amygdala demonstrated greater inverse connectivity during the 'Reappraise' condition relative to the 'Experience' condition. The only regions exhibiting significant age differences were the left IFG and the left superior temporal gyrus, for which greater regulation-related activation was observed in younger adults. Controlling for age, increased performance on measures of cognition predicted greater regulation-related decreases in amygdala activation. Thus, while older and younger adults use similar brain structures for emotion regulation and experience, the functional efficacy of those structures depends on underlying cognitive ability.

Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. fMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral PFC demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information.

Behavioral data have shown that attractive faces are better remembered but the neural mechanisms of this effect are largely unknown. To investigate this issue, female participants were scanned with event-related functional MRI (fMRI) while rating the attractiveness of male faces. Memory for the faces was tested after fMRI scanning and was used to identify successful encoding activity (subsequent memory paradigm). As expected, attractive faces were remembered better than other faces. The study yielded three main fMRI findings. First, activity in the right orbitofrontal cortex increased linearly as a function of attractiveness ratings. Second, activity in the left hippocampus increased as a function of subsequent memory (subsequent misses

The Beauty-is-Good stereotype refers to the assumption that attractive people possess sociably desirable personalities and higher moral standards. The existence of this bias suggests that the neural mechanisms for judging facial attractiveness and moral goodness overlap. To investigate this idea, we scanned participants with functional magnetic resonance imaging while they made attractiveness judgments about faces and goodness judgments about hypothetical actions. Activity in the medial orbitofrontal cortex increased as a function of both attractiveness and goodness ratings, whereas activity in the insular cortex decreased with both attractiveness and goodness ratings. Within each of these regions, the activations elicited by attractiveness and goodness judgments were strongly correlated with each other, supporting the idea of similar contributions of each region to both judgments. Moreover, activations in orbitofrontal and insular cortices were negatively correlated with each other, suggesting an opposing relationship between these regions during attractiveness and goodness judgments. These findings have implications for understanding the neural mechanisms of the Beauty-is-Good stereotype.

Although people do not normally try to remember associations between faces and physical contexts, these associations are established automatically, as indicated by the difficulty of recognizing familiar faces in different contexts ("butcher-on-the-bus" phenomenon). The present fMRI study investigated the automatic binding of faces and scenes. In the face-face (F-F) condition, faces were presented alone during both encoding and retrieval, whereas in the face/scene-face (FS-F) condition, they were presented overlaid on scenes during encoding but alone during retrieval (context change). Although participants were instructed to focus only on the faces during both encoding and retrieval, recognition performance was worse in the FS-F than in the F-F condition ("context shift decrement" [CSD]), confirming automatic face-scene binding during encoding. This binding was mediated by the hippocampus as indicated by greater subsequent memory effects (remembered > forgotten) in this region for the FS-F than the F-F condition. Scene memory was mediated by right parahippocampal cortex, which was reactivated during successful retrieval when the faces were associated with a scene during encoding (FS-F condition). Analyses using the CSD as a regressor yielded a clear hemispheric asymmetry in medial temporal lobe activity during encoding: Left hippocampal and parahippocampal activity was associated with a smaller CSD, indicating more flexible memory representations immune to context changes, whereas right hippocampal/rhinal activity was associated with a larger CSD, indicating less flexible representations sensitive to context change. Taken together, the results clarify the neural mechanisms of context effects on face recognition.

Among the most fundamental issues in cognitive neuroscience is how the brain may be organized into process-specific and stimulus-specific regions. In the episodic memory domain, most functional neuroimaging studies have focused on the former dimension, typically investigating the neural correlates of various memory processes. Thus, there is little information about what role stimulus-specific brain regions play in successful memory processes. To address this issue, the present event-related fMRI study used a factorial design to focus on the role of stimulus-specific brain regions, such as the fusiform face area (FFA) and parahippocampal place area (PPA) in successful encoding and retrieval processes. Searching within regions sensitive to faces or places, we identified areas similarly involved in encoding and retrieval, as well as areas differentially involved in encoding or retrieval. Finally, we isolated regions associated with successful memory, regardless of stimulus and process type. There were three main findings. Within face sensitive regions, anterior medial PFC and right FFA displayed equivalent encoding and retrieval success processes whereas left FFA was associated with successful encoding rather than retrieval. Within place sensitive regions, left PPA displayed equivalent encoding and retrieval success processes whereas right PPA was associated with successful encoding rather than retrieval. Finally, medial temporal and prefrontal regions were associated with general memory success, regardless of stimulus or process type. Taken together, our results clarify the contribution of different brain regions to stimulus- and process-specific episodic memory mechanisms.

We used functional magnetic resonance imaging (fMRI) to determine whether depressed (vs non-depressed) adults showed differences in cortical activation in response to stimuli representing personal goals. Drawing upon regulatory focus theory as well as previous research, we predicted that depressed patients would manifest attenuated left orbitofrontal cortex (OFC) activation in response to their own promotion goals as well as exaggerated right OFC activation in response to their own prevention goals. Unmedicated adults with major depression (n = 22) and adults with no history of affective disorder (n = 14) completed questionnaires and a personal goal interview. Several weeks later, they were scanned during a judgment task which (unknown to them) included stimuli representing their promotion and prevention goals. Both groups showed similar patterns of task-related activation. Consistent with predictions, patients showed significantly decreased left OFC and increased right OFC activation compared to controls on trials in which they were exposed incidentally to their promotion and prevention goals, respectively. The results suggest that depression involves dysfunction in processing two important types of personal goals. The findings extend models of the etiology of depression to incorporate cognitive and motivational processes underlying higher order goal representation and ultimately may provide an empirical basis for treatment matching.

Compared to young adults, older adults show not only a reduction in true memories but also an increase in false memories. We investigated the neural bases of these age effects using functional magnetic resonance imaging and a false memory task that resembles the Deese-Roediger-McDermott (DRM) paradigm. Young and older participants were scanned during a word recognition task that included studied words and new words that were strongly associated with studied words (critical lures). During correct recognition of studied words (true memory), older adults showed weaker activity than young adults in the hippocampus but stronger activity than young adults in the retrosplenial cortex. The hippocampal reduction is consistent with age-related deficits in recollection, whereas the retrosplenial increase suggests compensatory recruitment of alternative recollection-related regions. During incorrect recognition of critical lures (false memory), older adults displayed stronger activity than young adults in the left lateral temporal cortex, a region involved in semantic processing and semantic gist. Taken together, the results suggest that older adults' deficits in true memories reflect a decline in recollection processes mediated by the hippocampus, whereas their increased tendency to have false memories reflects their reliance on semantic gist mediated by the lateral temporal cortex.

Previous functional neuroimaging studies of temporal-order memory have investigated memory for laboratory stimuli that are causally unrelated and poor in sensory detail. In contrast, the present functional magnetic resonance imaging (fMRI) study investigated temporal-order memory for autobiographical events that were causally interconnected and rich in sensory detail. Participants took photographs at many campus locations over a period of several hours, and the following day they were scanned while making temporal-order judgments to pairs of photographs from different locations. By manipulating the temporal lag between the two locations in each trial, we compared the neural correlates associated with reconstruction processes, which we hypothesized depended on recollection and contribute mainly to short lags, and distance processes, which we hypothesized to depend on familiarity and contribute mainly to longer lags. Consistent with our hypotheses, parametric fMRI analyses linked shorter lags to activations in regions previously associated with recollection (left prefrontal, parahippocampal, precuneus, and visual cortices), and longer lags with regions previously associated with familiarity (right prefrontal cortex). The hemispheric asymmetry in prefrontal cortex activity fits very well with evidence and theories regarding the contributions of the left versus right prefrontal cortex to memory (recollection vs. familiarity processes) and cognition (systematic vs. heuristic processes). In sum, using a novel photo-paradigm, this study provided the first evidence regarding the neural correlates of temporal-order for autobiographical events.

Compared to young, older adults are more likely to forget events that occurred in the past as well as remember events that never happened. Previous studies examining false memories and aging have shown that these memories are more likely to occur when new items share perceptual or semantic similarities with those presented during encoding. It is theorized that decreased item-specific encoding and increased gist encoding contribute to these age differences in memory performance. The current study used a modified version of the Deese-Roediger-McDermott (DRM) paradigm to investigate the neural correlates of true and false memory encoding. Results indicated that, compared to young, older adults showed reduced activity in medial temporal lobes (MTL), left ventrolateral prefrontal cortex (VLPFC), and visual cortices associated with subsequent true memories. Despite these decreases older adults showed increased activity in right VLPFC and left superior temporal gyrus (STG) for subsequent true memories. Age-related increases in STG were also associated with subsequent false memories. Results support the theory that older adults engage in less item-specific encoding and greater gist encoding, and that these increases in gist encoding support both subsequent true and false memories. Furthermore, results extend findings of reduced frontal asymmetry in aging, often found in block designs, to the subsequent memory paradigm. Results suggest that greater bilateral frontal activity during encoding in aging are not just task-related, but may be associated with subsequent successful memory performance.

Regulatory focus theory [Higgins, E. T. Beyond pleasure and pain. American Psychologist, 52, 1280-1300, 1997] postulates two social-cognitive motivational systems, the promotion and prevention systems, for self-regulation of goal pursuit. However, the neural substrates of promotion and prevention goal activation remain unclear. Drawing on several literatures, we hypothesized that priming promotion versus prevention goals would activate areas in the left versus right prefrontal cortex (PFC), respectively, and that activation in these areas would be correlated with individual differences in chronic regulatory focus. Sixteen participants underwent functional magnetic resonance imaging while engaged in a depth-of-processing task, during which they were exposed incidentally to their own promotion and prevention goals. Task-related cortical activation was consistent with previous studies. At the same time, incidental priming of promotion goals was associated with left orbital PFC activation, and activation in this area was stronger for individuals with a chronic promotion focus. Findings regarding prevention goal priming were not consistent with predictions. The data illustrate the centrality of self-regulation and personal goal pursuit within the multilayered process of social cognition.

Using event-related functional magnetic resonance imaging, we identified brain regions involved in successful relational memory (RM) during encoding and retrieval for semantic and perceptual associations or in general, independent of phase and content. Participants were scanned while encoding and later retrieving associations between pairs of words (semantic RM) or associations between words and fonts (perceptual RM). Encoding success activity (ESA) was identified by comparing study-phase activity for items subsequently remembered (hits) versus forgotten (misses) and retrieval success activity (RSA) by comparing test-phase activity for hits versus misses. The study yielded three main sets of findings. First, ESA-RSA differences were found within the medial temporal lobes (MTLs) and within the prefrontal cortex (PFC). Within the left MTL, ESA was greater in the anterior hippocampus, and RSA was greater in the posterior parahippocampal cortex/hippocampus. This finding is consistent with the notion of an encoding-retrieval gradient along the longitudinal MTL axis. Within the left PFC, ESA was greater in ventrolateral PFC, and RSA was greater in dorsolateral and anterior PFC. This is the first evidence of a dissociation in successful encoding and retrieval activity within left PFC. Second, consistent with the transfer-appropriate processing principle, some ESA regions were reactivated during RSA in a content-specific manner. For semantic RM, these regions included the left ventrolateral PFC, whereas for perceptual RM, they included occipitoparietal and right parahippocampal regions. Finally, only one region in the entire brain was associated with RM in general (i.e., for both semantic and perceptual ESA and RSA): the left hippocampus. This finding highlights the fundamental role of the hippocampus in RM.

Functional neuroimaging studies of episodic memory retrieval generally measure brain activity while participants remember items encountered in the laboratory ("controlled laboratory condition") or events from their own life ("open autobiographical condition"). Differences in activation between these conditions may reflect differences in retrieval processes, memory remoteness, emotional content, retrieval success, self-referential processing, visual/spatial memory, and recollection. To clarify the nature of these differences, a functional MRI study was conducted using a novel "photo paradigm," which allows greater control over the autobiographical condition, including a measure of retrieval accuracy. Undergraduate students took photos in specified campus locations ("controlled autobiographical condition"), viewed in the laboratory similar photos taken by other participants (controlled laboratory condition), and were then scanned while recognizing the two kinds of photos. Both conditions activated a common episodic memory network that included medial temporal and prefrontal regions. Compared with the controlled laboratory condition, the controlled autobiographical condition elicited greater activity in regions associated with self-referential processing (medial prefrontal cortex), visual/spatial memory (visual and parahippocampal regions), and recollection (hippocampus). The photo paradigm provides a way of investigating the functional neuroanatomy of real-life episodic memory under rigorous experimental control.

We propose a new hypothesis concerning the lateralization of prefrontal cortex (PFC) activity during verbal episodic memory retrieval. The hypothesis states that the left PFC is differentially more involved in semantically guided information production than is the right PFC, and that the right PFC is differentially more involved in monitoring and verification than is the left PFC. This "production-monitoring hypothesis" differs from the existing "systematic-heuristic hypothesis," which proposes that the left PFC is primarily involved in systematic retrieval operations, and the right PFC in heuristic retrieval operations. To compare the two hypotheses, we measured PFC activity using positron emission tomography (PET) during the performance of four episodic retrieval tasks: stem cued recall, associative cued recall, context recognition (source memory), and item recognition. Recall tasks emphasized production processes, whereas recognition tasks emphasized monitoring processes. Stem cued recall and context-recognition tasks underscored systematic operations, whereas associative cued recall and item-recognition tasks underscored heuristic operations. Consistent with the production-monitoring hypothesis, the left PFC was more activated for recall than for recognition tasks and the right PFC was more activated for recognition than for recall tasks. Inconsistent with the systematic-heuristic hypothesis, the left PFC was more activated for heuristic than for systematic tasks and the right PFC showed the converse result. Additionally, the study yielded activation differences outside the PFC. In agreement with a previous recall/recognition PET study, anterior cingulate, cerebellar, and striatal regions were more activated for recall than for recognition tasks, and the converse occurred for posterior parietal regions. A right medial temporal lobe region was more activated for stem cued recall and context recognition than for associative cued recall and item recognition, possibly reflecting perceptual integration. In sum, the results provide evidence for the production-monitoring hypothesis and clarify the role of different brain regions typically activated in PET and functional magnetic resonance imaging (fMRI) studies of episodic retrieval.

Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribution of the PFC regions and the architecture of memory.

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.

In all cognitive tasks, general task-related processes operate throughout a given task on all items, whereas specific item-related processes operate differentially on individual items. In typical functional neuroimaging experiments, these two sets of processes have usually been confounded. Herein we report a combined positron emission tomography and event-related potential (ERP) experiment that was designed to distinguish between neural correlates of task-related and item-related processes of memory retrieval. Two retrieval tasks, episodic and semantic, were crossed with episodic (old/new) and semantic (living/nonliving) properties of individual items to yield evidence of regional brain activity associated with task-related processes, item-related processes, and their interaction. The results showed that episodic retrieval task was associated with increased blood flow in right prefrontal and posterior cingulate cortex, as well as with a sustained right-frontopolar-positive ERP, but that the semantic retrieval task was associated with left frontal and temporal lobe activity. Retrieval of old items was associated with increased blood flow in the left medial temporal lobe and with a brief late positive ERP component. The results provide converging hemodynamic and electrophysiological evidence for the distinction of task- and item-related processes, show that they map onto spatially and temporally distinct patterns of brain activity, and clarify the hemispheric encoding/retrieval asymmetry (HERA) model of prefrontal encoding and retrieval asymmetry.

Age-related differences in brain activity may reflect local neural changes in the regions involved or they may reflect a more global transformation of brain function. To investigate this issue, we applied structural equation modeling to the results of a positron emission tomography (PET) study in which young and old adults encoded and recalled word pairs. In the young group there was a shift from positive interactions involving the left prefrontal cortex during encoding to positive interactions involving the right prefrontal cortex during recall, whereas in the old group frontal interactions were mixed during encoding and bilaterally positive during recall. The present results suggest that age-related changes in neural activation are partly due to age-related changes in effective connectivity in the neural network underlying the task.

Recollecting a past episode involves remembering not only what happened but also when it happened. We used positron emission tomography (PET) to directly contrast the neural correlates of item and temporalorder memory. Subjects studied a list of words and were then scanned while retrieving information about what words were in the list or when they occurred within the list. Item retrieval was related to increased neural activity in medial temporal and basal forebrain regions, whereas temporal-order retrieval was associated with activations in dorsal prefrontal, cuneus/precuneus, and right posterior parietal regions. The dissociation between temporal and frontal lobe regions confirms and extends previous lesion data. The results show that temporal-order retrieval involves a network of frontal and posterior brain regions.

Positron emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.